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Coordinated responses of natural anticoagulants to allogeneic stem cell transplantation and acute GVHD – A longitudinal study

Przybyla, Beata; Pinomäki, Anne; Petäjä, Jari; Joutsi-Korhonen, Lotta; Strandberg, Karin LU ; Hillarp, Andreas LU ; Öhlin, Ann Kristin LU ; Ruutu, Tapani; Volin, Liisa and Lassila, Riitta (2017) In PLoS ONE 12(12).
Abstract

Background Allogeneic stem cell transplantation (SCT) enhances coagulation via endothelial perturbation and inflammation. Role of natural anticoagulants in interactions between coagulation and inflammation as well as in acute graft-versus-host disease (GVHD) are not well known. The purpose of this study was to define changes in natural anticoagulants over time in association with GVHD. Patients and methods This prospective study included 30 patients who received grafts from siblings (n = 19) or unrelated donors (n = 11). Eight patients developed GVHD. Standard clinical assays were applied to measure natural anticoagulants, represented by protein C (PC), antithrombin (AT), protein S (PS), complex of activated PC with its inhibitor... (More)

Background Allogeneic stem cell transplantation (SCT) enhances coagulation via endothelial perturbation and inflammation. Role of natural anticoagulants in interactions between coagulation and inflammation as well as in acute graft-versus-host disease (GVHD) are not well known. The purpose of this study was to define changes in natural anticoagulants over time in association with GVHD. Patients and methods This prospective study included 30 patients who received grafts from siblings (n = 19) or unrelated donors (n = 11). Eight patients developed GVHD. Standard clinical assays were applied to measure natural anticoagulants, represented by protein C (PC), antithrombin (AT), protein S (PS), complex of activated PC with its inhibitor (APC-PCI) and by markers of endothelial activation: Factor VIII coagulant activity (FVIII:C) and soluble thrombomodulin (s-TM) at 6–8 time points over three months. Results Overall, PC, AT and FVIII:C increased in parallel after engraftment. Significant correlations between PC and FVIII:C (r = 0.64–0.82, p<0.001) and between PC and AT (r = 0.62–0.81, p<0.05) were observed at each time point. Patients with GVHD had 21% lower PC during conditioning therapy and 55% lower APC-PCI early after transplantation, as well as 37% higher values of s-TM after engraftment. The GVHD group had also increases of PC (24%), FVIII: C (28%) and AT (16%) three months after transplantation. Conclusion The coordinated activation of natural anticoagulants in our longitudinal study indicates the sustained ability of adaptation to endothelial and inflammatory activation during allogenic SCT treatment. The suboptimal control of coagulation by natural anticoagulants at early stage of SCT may contribute to onset of GVHD.

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published
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PLoS ONE
volume
12
issue
12
publisher
Public Library of Science
external identifiers
  • scopus:85039167620
  • wos:000418651500023
ISSN
1932-6203
DOI
10.1371/journal.pone.0190007
language
English
LU publication?
yes
id
92b8a99c-7942-4b68-8022-52093ed35ca6
date added to LUP
2018-01-08 10:27:43
date last changed
2018-01-16 13:29:26
@article{92b8a99c-7942-4b68-8022-52093ed35ca6,
  abstract     = {<p>Background Allogeneic stem cell transplantation (SCT) enhances coagulation via endothelial perturbation and inflammation. Role of natural anticoagulants in interactions between coagulation and inflammation as well as in acute graft-versus-host disease (GVHD) are not well known. The purpose of this study was to define changes in natural anticoagulants over time in association with GVHD. Patients and methods This prospective study included 30 patients who received grafts from siblings (n = 19) or unrelated donors (n = 11). Eight patients developed GVHD. Standard clinical assays were applied to measure natural anticoagulants, represented by protein C (PC), antithrombin (AT), protein S (PS), complex of activated PC with its inhibitor (APC-PCI) and by markers of endothelial activation: Factor VIII coagulant activity (FVIII:C) and soluble thrombomodulin (s-TM) at 6–8 time points over three months. Results Overall, PC, AT and FVIII:C increased in parallel after engraftment. Significant correlations between PC and FVIII:C (r = 0.64–0.82, p&lt;0.001) and between PC and AT (r = 0.62–0.81, p&lt;0.05) were observed at each time point. Patients with GVHD had 21% lower PC during conditioning therapy and 55% lower APC-PCI early after transplantation, as well as 37% higher values of s-TM after engraftment. The GVHD group had also increases of PC (24%), FVIII: C (28%) and AT (16%) three months after transplantation. Conclusion The coordinated activation of natural anticoagulants in our longitudinal study indicates the sustained ability of adaptation to endothelial and inflammatory activation during allogenic SCT treatment. The suboptimal control of coagulation by natural anticoagulants at early stage of SCT may contribute to onset of GVHD.</p>},
  articleno    = {e0190007},
  author       = {Przybyla, Beata and Pinomäki, Anne and Petäjä, Jari and Joutsi-Korhonen, Lotta and Strandberg, Karin and Hillarp, Andreas and Öhlin, Ann Kristin and Ruutu, Tapani and Volin, Liisa and Lassila, Riitta},
  issn         = {1932-6203},
  language     = {eng},
  month        = {12},
  number       = {12},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Coordinated responses of natural anticoagulants to allogeneic stem cell transplantation and acute GVHD – A longitudinal study},
  url          = {http://dx.doi.org/10.1371/journal.pone.0190007},
  volume       = {12},
  year         = {2017},
}